Development and validation of a dried blood spots assay for metabolic profiling of ginsenosides using ultra-high performance liquid chromatography-mass spectrometry.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C.A. Meyer., a famous and valuable traditional Chinese medicine with thousand years of history for its healthcare and therapeutic effects. It is necessary and meaningful to study the pharmacokinetic behavior of ginsenosides in vivo as they are the most active components. Dried blood spots (DBS) are a mature and advanced blood collection method with meet the needs for the measurement of numerous analytes. AIM OF THE STUDY: This study aimed to explore the feasibility on DBS in the metabolic profile analysis of complex herbal products. MATERIALS AND METHODS: An ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) method was developed and validated for the determination of ginsenosides. The preparation of DBS samples was conducted by spiking the whole blood with analytes to obtain 20 µL of blood spots on Whatman 903 collection card. A punched dish of 10 mm in diameter was extracted with 70 % methanol aqueous solution, digoxin was used as an internal standard. Target compounds were separated on a Waters T3 column (2.1 × 100 mm, 1.8 µm) with acetonitrile and water (0.1 % formic acid) at a flow rate of 0.4 mL/min. RESULTS: The various ginsenosides showed good linearity in the range of 1-2000 ng/mL. The extraction recoveries and matrix effects of the target analytes were above 82.2%. The intra- and inter-batch accuracy and precision were within the limits of ≤15% for all tested concentrations. Moreover, the collected dried blood spot samples could be stably stored at room temperature for 14 days and 4 °C for 1 month without being affected. And it is delightful that the DBS-based analysis is compatible or even superior to the conventional protein precipitation in terms of sensitivity, linearity, and stability. In particular, the target analytes are stable in the DBS sampling under normal storing condition and the sensitivity for some trace metabolites of ginsenosides, such as 20(S)-Rg3, 20(R)-Rg3, F1, Rk1, Rg5, etc. increases 3-4 folds as evaluated by LLOQ. CONCLUSIONS: The established method was successfully applied to pharmacokinetic studies of ginseng extract in mice, this suggests a more feasible strategy for pharmacokinetic study of traditional and natural medicines both in animal tests and clinical trials.

Study on the mechanism of Shuganzhi Tablet against nonalcoholic fatty liver disease and lipid regulation effects of its main substances in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Shuganzhi Tablet (SGZT) originates from a famous traditional Chinese herbal formula Chaihu Decoction which can be applied to treat liver diseases, however, the pharmacodynamic mechanism of SGZT needs to be evaluated. AIM OF THIS STUDY: To study the mechanism of SGZT in the treatment of non-alcoholic fatty liver disease (NAFLD), and screen out its effective ingredients. MATERIALS AND METHODS: In this study, firstly, the main components of SGZT were analyzed qualitatively. And a rat model of NAFLD was established by feeding high-fat diet. Serum biochemical indexes and liver pathological analysis were used to evaluate the pharmacodynamic effect of SGZT in the treatment of NAFLD. In order to explore the pharmacodynamic mechanism, proteomics and metabolomics analysis were used. Western blotting was used to verify the expression of important differential proteins. And L02 cells were treated with free fatty acids (FFA) and the main substances of SGZT to establish the cell model of NAFLD in vitro and to reveal the pharmacodynamic substance of SGZT. RESULTS: Twelve components were detected in SGZT, and according to the results of serum biochemical indexes and liver pathological analysis, SGZT could effectively treat NAFLD. Combined with the results of bioinformatics analysis, we found that 133 differentially expressed proteins were reversed in liver samples of rats treated with SGZT. The important proteins in PPAR signaling pathway, steroid biosynthesis, cholesterol metabolism and fatty acid metabolism were mainly regulated to maintain cholesterol homeostasis and improve lipid metabolism. SGZT also affected various metabolites in rat liver, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and taurine. In addition, the main components contained in SGZT (hesperidin, polydatin, naringin, emodin, specnuezhenide, saikosaponin A) and a metabolite (resveratrol) could significantly reduce FFA-induced intracellular lipid accumulation. CONCLUSION: SGZT effectively treated NAFLD, and PPAR-γ, Acsl4, Plin2 and Fads1 may be the main targets of SGZT. And Fads1-EPA/DHA-PPAR-γ may be the potential pharmacodynamic pathway. Cell experiments in vitro revealed that the main components of SGZT and their metabolites, such as hesperidin, polydatin, naringin, emodin, specnuezhenide, saikosaponin A and resveratrol may be the main components of its efficacy. Further research is needed to reveal and validate the pharmacodynamic mechanism.

Family physicians collaborating for health system integration: a scoping review.

BACKGROUND: In Canada, Ontario Health Teams (OHTs) are a new model for integrated healthcare. Core to OHTs are family physicians (FPs) and their ability to collaborate with other FPs and healthcare providers. Whereas the factors for intra-organizational collaboration have been well-studied, inter-organizational collaboration between FPs and other healthcare organizations as an integrated care network, are less understood. This paper aims to explore the structural factors, processes, and theoretical frameworks that support FPs' collaboration for integrated healthcare. METHODS: A scoping review was undertaken based on Joanna Briggs Institute (JBI) methodology for scoping review and using the Preferred Reporting Items for Systematic Review and Meta-Analysis for Scoping Review (PRISMA_ScR) checklist. A search for academic and relevant grey literature published between 2000-2021 was conducted across databases (MEDLINE, EMBASE, EBSCOhost).Thematic analysis was used to identify the key findings of the selected studies. RESULTS: Thirty-two studies were included as eligible for this review. Three structural components were identified as critical to FPs' successful participation in inter-organizational partnerships: (1) shared vision/values, (2) leadership by FPs, and (3) defined decision-making procedures. Also, three processes were identified: (1) effective communication, (2) a collective sense of motivation for change, and (3) relationships built on trust. Three theoretical frameworks provided insight into collaborative initiatives: (1) Social Identity Approach, (2) framework of interprofessional collaboration, and (3) competing values framework. CONCLUSION: FPs hold unique positions in healthcare and this review is the first to synthesize the best evidence for building collaborations between FPs and other healthcare sectors. These findings will inform collaboration strategies for healthcare integration, including with OHTs.

Metabolite Profiling of Swertia cincta Extract in Rats and Pharmacokinetics Study of Three Bioactive Compounds Using UHPLC-MS/MS.

Swertia cincta, a plant of the genus Swertia in Gentianceae, has "heat-clearing" and detoxifying effects that normalize the gallbladder function in the treatment of jaundice. Although numerous studies on Swertia cincta have been performed, the absorption and pharmacokinetic behaviors remain unclear. In this study, the compounds of Swertia cincta in serum, bile, feces, and urine of rats were analyzed using a ultra-high-performance liquid chromatography-tandem mass spectrometry. A total of 9 prototype components and 48 metabolites were detected in biological samples. Furthermore, we determined the main components absorbed in the blood of Swertia cincta and established a method for simultaneously determining these components (sweroside, swertiamarin, and gentiopicroside) in positive ionization mode within 6 min. The quantitative method was successfully applied for the multiple-component pharmacokinetic study of Swertia cincta.

Clinical effects of fractional carbon dioxide laser combined with minimally invasive scar release in the treatment of post-acne atrophic scars / 中华烧伤杂志

Objective: To explore the clinical effects of fractional carbon dioxide laser combined with minimally invasive scar release in the treatment of post-acne atrophic scars. Methods: A retrospectively observational study was conducted. From January to June 2021, 60 patients with grade 3 and 4 post-acne atrophic scars who met the inclusion criteria were admitted to the First Affiliated Hospital of Henan University of Traditional Chinese Medicine. According to the adopted treatment methods, 30 patients treated with fractional carbon dioxide laser combined with minimally invasive scar release were included in combined treatment group (19 males and 11 females, aged (26±4) years), and 30 patients treated with fractional carbon dioxide laser alone were included in laser alone group (18 males and 12 females, aged (25±6) years). All the patients received the treatment once every two months, totally 3 times. Before the first treatment and 2 months after the last treatment, the scars were assessed by échelle d'évaluation clinique des cicatrices d'acné (ECCA). In 2 months after the last treatment, the curative effect was evaluated and the total effective rate was calculated according to the ECCA score. The adverse reactions of patients during the treatment were recorded. Data were statistically analyzed with independent sample t test, Wilcoxon rank-sum test, Mann-Whitney U test, chi-square test, and Fisher's exact probability test. Results: Before the first treatment, the ECCA scores of patients in the two groups were similar (P>0.05). In 2 months after the last treatment, the ECCA scores of patients in combined treatment group were significantly lower than those of laser alone group (Z=-2.89, P<0.05). The ECCA scores of patients in combined treatment group and laser alone group in 2 months after the last treatment were both significantly lower than those before the first treatment (with Z values of -4.81 and -4.79, respectively, P<0.05). In 2 months after the last treatment, the treatment in laser alone group cured the scars in 2 patients, and were markedly effective in 13 patients, effective in 7 patients, and ineffective in 8 patients; the treatment in combined treatment group cured the scars in 4 patients, and were markedly effective in 22 patients, effective in 3 patients, and ineffective in one patients. The total effective rate of scar treatment in combined treatment group (96.67%, 29/30) was significantly higher than 73.33% (22/30) in laser alone group (P<0.05). During treatment, in combined treatment group, 3 patients had pain, one patient had redness and swelling, and one patient had pigmentation. In laser alone group, one patient had pain, and 2 patients had pigmentation. No infection occurred in the wounds of all the patients in the two groups. Conclusions: Compared with fractional carbon dioxide laser alone, fractional carbon dioxide laser combined with minimally invasive scar release for post-acne atrophic scars can result in a higher total effective rate, with simple operation and good effect, so it is worthy of clinical application.

The Application of Complementary and Alternative Medicine in Polycystic Ovary Syndrome Infertility.

Polycystic ovary syndrome (PCOS) is a lifelong reproductive endocrine disease, which is the most common cause of anovular infertility. Modern medicine mainly treats infertile patients with PCOS by improving living habits, ovulation induction therapy, and assisted reproductive technology (ART), but the effect is not satisfied. Complementary alternative medicine (CAM) has conspicuous advantages in the treatment of PCOS infertility due to its good clinical efficacy, wide mechanism of action, and no obvious adverse reactions, but its safety and effectiveness in the treatment of PCOS infertility have not been proved. Based on the existing clinical and experimental studies, this paper looks for the therapeutic effect and the mechanism behind it, and explores the safety and effectiveness of its treatment in PCOS infertility, in order to provide reference for future clinical treatment and experimental research.

Swertiamarin, an active iridoid glycoside from Swertia pseudochinensis H. Hara, protects against alpha-naphthylisothiocyanate-induced cholestasis by activating the farnesoid X receptor and bile acid excretion pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Swertiamarin (SW), which belongs to iridoid glycosides, is one of the main components of Swertia plants in Gentianaceae family, including Swertia pseudochinensis H. Hara and Swertia mileensis T. N. Ho et W. L. Shi. There are mainly used in traditional Chinese medicine for the treatment of hepatic and biliary disease such as jaundice. AIM OF THIS STUDY: This experiment aimed to explore the protective mechanism of SW on cholestasis induced by alpha-naphthylisothiocyanate in rats. MATERIALS AND METHODS: Healthy rats were randomly divided into the control, model (ANIT, 50 mg/kg), ursodeoxycholic acid (UDCA, 80 mg/kg), and low-dose (SW, 80 mg/kg), medium-dose (SW, 100 mg/kg), and high-dose (SW, 150 mg/kg) groups. The hepatic protective effect of SW was preliminarily evaluated by measurement of serum biochemical indicators and liver morphological evaluation. Moreover, metabolomics and proteomics analysis were used to explore the protective mechanism of SW on cholestasis. The expression of related proteins was determined by Western blot and polymerase chain reaction, and the important proteins were verified by cell experiments in vitro. RESULTS: SW (100 mg/kg) can reduce the serum levels of the model group. The hepatocyte of the medium-dose treatment group was arranged neatly without evident inflammation. SW can partially reverse the changes in cholestasis metabolites, such as taurocholic acid, SM (d18:1/16:0), all-trans-retinoic acid and other products of rats. The main metabolic pathways affected were primary bile acid synthesis, glycerophospholipid metabolism, sphingolipid metabolism and retinol metabolism. SW medium-dose treatment group showed effective reversal of 25 related proteins and it can remarkably reduce the contents of NTCP and CYP27A1 in rat liver and increase the protein expressions of CYP7A1, CYP8B1, bile salt export pump, multidrug resistance-associated protein and FXR. CONCLUSIONS: SW can alleviate ANIT-induced cholestasis, which by activating the farnesoid X receptor and bile acid excretion pathway.

Treatment of bilateral granulomatous lobular mastitis during lactation with traditional Chinese medicine: A case report.

BACKGROUND: Granulomatous lobular mastitis (GLM) is a type of benign chronic inflammatory disease that poses therapeutic challenges to healthcare providers. The diagnosis of GLM relies on tissue biopsy, and incorrect treatment may lead to delayed diagnosis, considerable aesthetic damage, and even mastectomy. CASE SUMMARY: We report the case of a 37-year-old Chinese woman who was lactating and had GLM in both breasts. At the time of treatment, the right breast had a mass of approximately 15 cm × 11 cm, which was hard and had poor mobility. Multiple skin ulcerations and pus spills were also observed on the surface of the breast. The left breast had a mass of about 13 cm × 9 cm, which was hard and had poor mobility. CONCLUSION: Herein, we report a case of bilateral GLM in a lactating woman that was successfully treated with traditional Chinese medicine (TCM), without the requirement for surgery or other treatments. Therefore, TCM may have advantages in the nonsurgical treatment of GLM.

Metabolite profiling of Shuganzhi tablets in rats and pharmacokinetics study of four bioactive compounds with liquid chromatography combined with electrospray ionization tandem mass spectrometry.

Shuganzhi Tablets (SGZT) is developed on the basis of a clinical empirical formula as a hospital preparation for the treatment of fatty liver. In this study, a rapid and highly sensitive LC-MS/MS method was established and validated for simultaneous determination of ginsenoside Re, ginsenoside Rg1, notoginsenoside R1, naringin, specnuezhenide, emodin, polydatin, hesperidin and saikosaponin A in rat plasma. Multiple reaction monitoring mode played an important role in simultaneous quantitative analysis of multiple components. The analytes were separated by the action of an ACQUITY UPLC® BEH C18 column (2.1 × 50 mm, 1.7 µm) in five minutes. The validated LC-MS/MS method was successfully applied to the pharmacokinetic analysis of hesperidin, emodin, polydatin and naringin of SGZT in rat plasma after administration. A UHPLC system couple with a quadrupole combined with time of flight mass spectrometer was used for qualitatively analyzing of the composition of SGZT and its metabolites in serum, urine, bile and feces of rats. The results showed that a total of 65 components were detected in rat biological samples, including 10 prototype components and 55 metabolites. It was speculated that the ingredients of SGZT experienced mainly the following reactions in rats: phase I reaction such as hydrolysis, oxidation, hydroxylation, carboxylation and dehydroxylation and phase Ⅱ reaction such as glucuronidation and sulfation. These results provide useful information for the further study of its active ingredients.

Identification of dihydrotanshinone I as an ERp57 inhibitor with anti-breast cancer properties via the UPR pathway.

Salvia miltiorrhiza (Danshen) is a well-known traditional Chinese medicine for treating various diseases, such as breast cancer. However, knowledge regarding its mechanisms is scant. Herein, the active ingredient dihydrotanshinone I (DHT) in Salvia miltiorrhiza extract (SME), which binds ERp57 was identified and verified by an enzymatic solid-phase method combined with LC-MS/MS. DHT potentially inhibited ERp57 activity and suppressed ERp57 expression at both the RNA and protein levels. Molecular docking simulation indicated that DHT could form a hydrogen bond with catalytic site of ERp57. Moreover, ERp57 overexpression decreased DHT-induced cytotoxicity in MDA-MB-231 cells. Thereafter, the signaling pathway downstream of ERp57 was investigated by Western blot analysis. The mechanistic study revealed that DHT treatment resulted in activation of endoplasmic reticulum (ER) stress, the unfolded protein response (UPR), and cellular apoptosis. In conclusion, our data implied that DHT targeted ERp57 for inhibition and induced ER stress and UPR activation, which in turn triggered breast cancer cell apoptosis.

Engineering Wafer-Scale Epitaxial Two-Dimensional Materials through Sapphire Template Screening for Advanced High-Performance Nanoelectronics.

In view of its epitaxial seeding capability, c-plane single crystalline sapphire represents one of the most enticing, industry-compatible templates to realize manufacturable deposition of single crystalline two-dimensional transition metal dichalcogenides (MX2) for functional, ultrascaled, nanoelectronic devices beyond silicon. Despite sapphire being atomically flat, the surface topography, structure, and chemical termination vary between sapphire terraces during the fabrication process. To date, it remains poorly understood how these sapphire surface anomalies affect the local epitaxial registry and the intrinsic electrical properties of the deposited MX2 monolayer. Therefore, molybdenum disulfide (MoS2) is deposited by metal-organic chemical vapor deposition (MOCVD) in an industry-standard epitaxial reactor on two types of c-plane sapphire with distinctly different terrace and step dimensions. Complementary scanning probe microscopy techniques reveal an inhomogeneous conductivity profile in the first epitaxial MoS2 monolayer on both sapphire templates. MoS2 regions with poor conductivity correspond to sapphire terraces with uncontrolled topography and surface structure. By intentionally applying a substantial off-axis cut angle (1° in this work), the sapphire terrace width and step height-and thus also surface structure-become more uniform across the substrate and MoS2 conducts the current more homogeneously. Moreover, these effects propagate into the extrinsic MoS2 device performance: the field-effect transistor variability reduces both within and across wafers at higher median electron mobility. Carefully controlling the sapphire surface topography and structure proves an essential prerequisite to systematically study and control the MX2 growth behavior and capture the influence on its structural and electrical properties.

The Effects of Static Magnetic Field on Orthodontic Tooth Movement in Mice.

The application of static magnetic field (SMF) has been considered an effective and noninvasive method to accelerate orthodontic tooth movement. The objective of this study was to explore the effects of SMF on orthodontic tooth movement in mice. A total of 105 Balb/c mice (body mass: 25-30 g) were divided into experimental group (SMF + force, 48), control group (force only, 48), and blank group (neither SMF nor force, 9). After the placement of orthodontic appliances, the experimental group was exposed to the SMF environment generated by Neodymium-iron-boron (NdFeB) magnets with an intensity of 20-204 mT. At 1, 3, 7, 14, 21, and 28 days after appliance insertion, eight animals in both experimental and control groups were sacrificed and the left maxillae were dissected to measure the distance of tooth movement, respectively. Meanwhile, the width of periodontal ligament (PDL), length of hyalinized zone, and the number of osteoclasts were evaluated by hematoxylin-eosin and tartrate-resistant acid phosphatase staining. We finally found that the experimental group demonstrated an enhanced rate and greater cumulative amount of tooth movement than the control group (0.2887 ± 0.0041 mm vs. 0.2114 ± 0.0089 mm, P < 0.05). On Days 7, 14, and 28, the experimental group also displayed a significantly greater width of PDL. Earlier formation and removal of the hyalinized zone, and significantly more osteoclasts were observed in the experimental group as well. The results suggested that SMF may be a promising nonsurgical intervention to accelerate orthodontic tooth movement. © 2021 Bioelectromagnetics Society.

Feedback on feedback: a two-way street between residents and preceptors.

BACKGROUND: Workplace-based assessment (WBA), foundational to competency-based medical education, relies on preceptors providing feedback to residents. Preceptors however get little timely, formative, specific, actionable feedback on the effectiveness of that feedback. Our study aimed to identify useful qualities of feedback for family medicine residents and to inform improving feedback-giving skills for preceptors in PGME training program. METHODS: This study employed a two-phase exploratory design. Phase 1 collected qualitative data from preceptor feedback given to residents through Field Notes (FNs) and quantitative data from residents who provided feedback to preceptor about the quality of the feedback given. Phase 2 employed focus groups to explore ways in which residents are willing to provide preceptors with constructive feedback about the quality of the feedback they receive. Descriptive statistics and a thematic approach were used for data analysis. FINDINGS: We collected 22 FNs identified by residents as being impactful to their learning; analysis of these FNs resulted in five themes. Functionality was then added to the electronic FNs allowing residents to indicate impactful feedback with a "Thumbs Up" icon. Over one year, 895 out of 8,496 FNs (11%) had a "Thumbs up" added, divided into reasons of: confirmation of learning (28.6%), practice improvement (21.2%), new learning (18.8%), motivation (17.7%), and evoking reflection (13.7%). Two focus groups (12 residents, convenience sampling) explored residents' perception of constructive feedback and willingness to also provide constructive feedback to preceptors. CONCLUSION: Adding constructive feedback to existing positive feedback choices will provide preceptors with holistic information about the impact of their feedback on learners, which, in turn, should allow them to provide more effective feedback to learners. However, power differential, relationship impact, and institutional support were concerns for residents that would need to be addressed for this to be optimally operationalized.

CONTEXTE: L'évaluation en milieu de travail (EMT), qui est à la base de la formation médicale fondée sur les compétences, repose sur la rétroaction donnée par les superviseurs aux résidents. En revanche, il est rare que les superviseurs reçoivent à leur tour, et en temps utile, une rétroaction formative, précise et pratique sur l'efficacité des commentaires qu'ils ont offerts. L'objectif de notre étude était de déceler les caractéristiques qu'un tel retour doit avoir pour être utile aux résidents en médecine familiale afin de guider l'amélioration des compétences en rétroaction des superviseurs de programmes d'éducation médicale postdoctorale. MÉTHODES: Nous avons utilisé un devis exploratoire en deux phases. Lors de la première phase, nous avons recueilli les données qualitatives à partir des commentaires fournis par les précepteurs aux résidents par le biais de feuilles de route (FR) et les données quantitatives de rétroactiondes résidents sur la qualité de la rétroaction qui leur a été offerte par les superviseurs. Dans la phase 2, des groupes de discussion ont été constitués pour explorer les moyens par lesquels les résidents sont prêts à fournir aux superviseurs une rétroaction constructive sur la qualité de la rétroaction qu'ils reçoivent. L'analyse des données a été faite à l'aide de statistiques descriptives et d'une approche thématique. RÉSULTATS: Les auteurs ont recueilli 22 feuilles de route (FR) qui, d'après les résidents, ont eu un effet sur leur apprentissage. L'analyse des FR a permis de relever cinq thèmes. Une fonctionnalité a par la suite été ajoutée aux FR électroniques, permettant aux résidents d'indiquer qu'une rétroaction a été efficace à l'aide d'un pictogramme « Pouce levé ¼. En un an, 895 des 8496 FR (11 %) ont reçu un « Pouce levé ¼ et les raisons qui l'expliquent sont réparties de la manière suivante : la rétroaction confirmait au résident ses acquis (28,6 %), elle l'aidait à améliorer sa pratique (21,2 %), elle lui apprenait quelque chose de nouveau (18,8 %), elle stimulait sa motivation (17,7 %) ou encore sa réflexion (13,7 %). Deux groupes de discussion (12 résidents, échantillon de convenance) ont exploré ce que les résidents perçoivent comme étant une rétroaction constructive, et s'ils sont prêts à fournir à leur tour un commentaire constructif aux superviseurs. CONCLUSION: Le fait d'ajouter des commentaires constructifs aux commentaires positifs renseignerait les superviseurs de manière plus complète sur l'effet qu'a eu leur rétroaction pour les apprenants, et les aiderait ainsi à améliorer l'efficacité des rétroactions qu'ils donnent. Cependant, pour mettre en place ce processus de manière optimale, il faut tenir compte des préoccupations qu'ont les résidents quant au déséquilibre de pouvoir, aux répercussions sur leur relation avec le superviseur et à l'appui de l'établissement.

Regulation of the Hippo Pathway by Phosphatidic Acid-Mediated Lipid-Protein Interaction.

The Hippo pathway plays a crucial role in organ size control and tumor suppression, but its precise regulation is not fully understood. In this study, we discovered that phosphatidic acid (PA)-related lipid signaling is a key regulator of the Hippo pathway. Supplementing PA in various Hippo-activating conditions activates YAP. This PA-related lipid signaling is involved in Rho-mediated YAP activation. Mechanistically, PA directly interacts with Hippo components LATS and NF2 to disrupt LATS-MOB1 complex formation and NF2-mediated LATS membrane translocation and activation, respectively. Inhibition of phospholipase D (PLD)-dependent PA production suppresses YAP oncogenic activities. PLD1 is highly expressed in breast cancer and positively correlates with YAP activation, suggesting their pathological relevance in breast cancer development. Taken together, our study not only reveals a role of PLD-PA lipid signaling in regulating the Hippo pathway but also indicates that the PLD-PA-YAP axis is a potential therapeutic target for cancer treatment.

Advances in the antitumor activities and mechanisms of action of steroidal saponins.

The steroidal saponins are one of the saponin types that exist in an unbound state and have various pharmacological activities, such as anticancer, anti-inflammatory, antiviral, antibacterial and nerves-calming properties. Cancer is a growing health problem worldwide. Significant progress has been made to understand the antitumor effects of steroidal saponins in recent years. According to reported findings, steroidal saponins exert various antitumor activities, such as inhibiting proliferation, inducing apoptosis and autophagy, and regulating the tumor microenvironment, through multiple related signaling pathways. This article focuses on the advances in domestic and foreign studies on the antitumor activity and mechanism of actions of steroidal saponins in the last five years to provide a scientific basis and research ideas for further development and clinical application of steroidal saponins.

Nitric Oxide Is Required for Melatonin-Enhanced Tolerance against Salinity Stress in Rapeseed (Brassica napus L.) Seedlings.

Although melatonin (N-acetyl-5-methoxytryptamine) could alleviate salinity stress in plants, the downstream signaling pathway is still not fully characterized. Here, we report that endogenous melatonin and thereafter nitric oxide (NO) accumulation was successively increased in NaCl-stressed rapeseed (Brassica napus L.) seedling roots. Application of melatonin and NO-releasing compound not only counteracted NaCl-induced seedling growth inhibition, but also reestablished redox and ion homeostasis, the latter of which are confirmed by the alleviation of reactive oxygen species overproduction, the decreases in thiobarbituric acid reactive substances production, and Na⁺/K⁺ ratio. Consistently, the related antioxidant defense genes, sodium hydrogen exchanger (NHX1), and salt overly sensitive 2 (SOS2) transcripts are modulated. The involvement S-nitrosylation, a redox-based posttranslational modification triggered by NO, is suggested. Further results show that in response to NaCl stress, the increased NO levels are strengthened by the addition of melatonin in seedling roots. Above responses are abolished by the removal of NO by NO scavenger. We further discover that the removal of NO does not alter endogenous melatonin content in roots supplemented with NaCl alone or together with melatonin, thus excluding the possibility of NO-triggered melatonin production. Genetic evidence reveals that, compared with wild-type Arabidopsis, the hypersensitivity to NaCl in nia1/2 and noa1 mutants (exhibiting null nitrate reductase activity and indirectly reduced endogenous NO level, respectively) cannot be rescued by melatonin supplementation. The reestablishment of redox homeostasis and induction of SOS signaling are not observed. In summary, above pharmacological, molecular, and genetic data conclude that NO operates downstream of melatonin promoting salinity tolerance.

Jolkinolide B inhibits glycolysis by downregulating hexokinase 2 expression through inactivating the Akt/mTOR pathway in non-small cell lung cancer cells.

Jolkinolide B (JB), a bioactive compound isolated from herbal medicine, has been found to inhibit tumor growth by altering glycolysis. However, whether glycolysis is influenced by JB in non-small cell lung cancer (NSCLC) cells and the mechanism remain unknown. The aim of the present study was to evaluate the effect of JB on the glycolysis in NSCLC cells and the underlying molecular mechanism. The results showed that JB treatment inhibited cell viability of A549 and H1299 cells in a concentration-dependent manner. JB reduced the glucose consumption, lactate production, and HK2 expression. The expressions of p-Akt and p-mTOR were also decreased by JB treatment. Knockdown of HK2 reduced glucose consumption and lactate production. Inhibition of the Akt/mTOR pathway decreased HK2 expression and inhibited glycolysis. In conclusion, the results indicated that JB inhibits glycolysis by down-regulating HK2 expression through inactivating the Akt/mTOR pathway in NSCLC cells, suggesting that JB might be a potential therapeutic agent for the treatment of NSCLC.

Advances in the antitumor activities and mechanisms of action of steroidal saponins / 中国天然药物

The steroidal saponins are one of the saponin types that exist in an unbound state and have various pharmacological activities, such as anticancer, anti-inflammatory, antiviral, antibacterial and nerves-calming properties. Cancer is a growing health problem worldwide. Significant progress has been made to understand the antitumor effects of steroidal saponins in recent years. According to reported findings, steroidal saponins exert various antitumor activities, such as inhibiting proliferation, inducing apoptosis and autophagy, and regulating the tumor microenvironment, through multiple related signaling pathways. This article focuses on the advances in domestic and foreign studies on the antitumor activity and mechanism of actions of steroidal saponins in the last five years to provide a scientific basis and research ideas for further development and clinical application of steroidal saponins.

Advances in the antitumor activities and mechanisms of action of steroidal saponins / 中国天然药物

The steroidal saponins are one of the saponin types that exist in an unbound state and have various pharmacological activities, such as anticancer, anti-inflammatory, antiviral, antibacterial and nerves-calming properties. Cancer is a growing health problem worldwide. Significant progress has been made to understand the antitumor effects of steroidal saponins in recent years. According to reported findings, steroidal saponins exert various antitumor activities, such as inhibiting proliferation, inducing apoptosis and autophagy, and regulating the tumor microenvironment, through multiple related signaling pathways. This article focuses on the advances in domestic and foreign studies on the antitumor activity and mechanism of actions of steroidal saponins in the last five years to provide a scientific basis and research ideas for further development and clinical application of steroidal saponins.

Advances of active ingredients of traditional Chinese medicine in the preven-tion and treatment of osteoarthritis / 中国药科大学学报

Osteoarthritis (OA),a common chronic degenerative joint disease,rises gradually with age,which seri-ously affects the quality of life of middle-aged and elderly patients. Currently,the therapeutic medications such as nonsteroidal anti-inflammatory drugs (NSAIDs)and analgesics might improve OA symptoms,but cannot prevent the development of OA. The active ingredients of traditional Chinese medicine (TCM)have unique advantages in the treatment of OA. This article reviews the research progress of active ingredients of TCM in the prevention and treatment of OA reported by domestic and foreign journals in the past five years from the aspects of inhibition of the secretion of inflammation-related factors,improvement of cartilage matrix synthesis and catabolic imbalance, inhibition of chondrocyte apoptosis,promotion of chondrocyte proliferation,and regulation of estrogen levels,with an attempt to provide a theoretical basis for the development of new drugs for OA.